Background: It has been reported that preformed donor-specific anti-human leukocyte antigen antibodies (DSAs) were associated with poor graft outcomes in kidney transplant recipients. To eliminate preformed DSAs, we desensitized DSA-positive patients by injecting rituximab and then performed plasmapheresis in those patients using a protocol for ABO-incompatible (ABO-I) transplant recipients. B-cell depletion with rituximab may influence T-cell responses to alloantigens since B-cells are effective antigen-presenting cells that are capable of activating donor-specific T-cells. It is also likely that the cytokine release syndrome, which is caused by rituximab, may enhance T-cell activation. In this study, we investigated the impact of pre-transplant desensitization with rituximab on the subsequent response of T-cells to alloantigens in DSA-positive kidney transplant recipients.

Methods: Fourteen DSA-positive patients of kidney allografts were employed in this study, while 26 DSA-negative ABO-I recipients of kidney allografts formed the control group that received a similar desensitization preconditioning with rituximab and plasmapheresis. To monitor the recipients' immune status, a mixed lymphocyte reaction assay using a CFSE-labeling technique was performed before and after desensitization.

Results: Before desensitization, there were no significant differences in the average stimulation index (SI) values for the responses of the CD4⁺ and CD8⁺ T-cells to donor stimuli between the two groups. However, after desensitization, the average SI values for the CD4⁺ T-cells were significantly higher in the DSA-positive patients than those in the DSA-negative ABO-I patients. Patients with high SI values were treated with rabbit thymocyte globulin (rATG), and neither antibody-mediated rejection nor severe acute cellular rejection was encountered in these patients after transplantation.

Conclusions: These findings demonstrate that B-cell depletion with rituximab exacerbates anti-donor CD4⁺ T-cell responses in DSA-positive organ transplant recipients. It might be possible that treatment with rituximab undesirably depletes specific B-cell subsets that could regulate T-cell responses to alloantigens. Although this issue is currently under investigation, T-cell responses could possibly be inhibited by rATG before or after desensitization to prevent ACR events.

CITATION INFORMATION: Tanaka A., Ide K., Tanaka Y., Ohira M., Tahara H., Shimizu S., Ohdan H. B-Cell Depletion with Rituximab Exacerbates Anti-Donor CD4⁺ T-Cell Responses in Patients with Donor-Specific Anti-Human Leukocyte Antigen Antibodies Am J Transplant. 2017;17 (suppl 3).

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